US8017797B2 - Method for producing phosphorus-containing α-keto acid - Google Patents

Method for producing phosphorus-containing α-keto acid Download PDF

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US8017797B2
US8017797B2 US12/530,022 US53002208A US8017797B2 US 8017797 B2 US8017797 B2 US 8017797B2 US 53002208 A US53002208 A US 53002208A US 8017797 B2 US8017797 B2 US 8017797B2
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formula
compound
existence
acid
following formula
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US20100063313A1 (en
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Nobuto Minowa
Nozomu Nakanishi
Masaaki Mitomi
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Meiji Seika Kaisha Ltd
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Meiji Seika Kaisha Ltd
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Assigned to MEIJI SEIKA KAISHA LTD. reassignment MEIJI SEIKA KAISHA LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MINOWA, NOBUTO, MITOMI, MASAAKI, NAKANISHI, NOZOMU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/301—Acyclic saturated acids which can have further substituents on alkyl

Definitions

  • the present invention relates to a method for producing 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid which is useful as a production intermediate of a herbicide; L-2-amino-4-(hydroxymethylphosphinyl)-butanoic acid (in the below, it is abbreviated as L-AMPB).
  • 3-(alkoxymethylphosphinyl)-propionic acid ester is synthesized such that methyldichlorophosphine is subjected to an addition reaction with acrylic acid, then the produced acid chloride is subjected to a reaction with alcohol (see non-patent documents 3 and 4).
  • the present invention is as follows.
  • R 1 representing C 1-4 alkyl group, arylmethyl group, or substituted arylmethyl group
  • R 2 represents C 1-4 alkyl group, arylmethyl group, or substituted arylmethyl group
  • a method for producing a compound of formula (6) as a step for producing the compound of formula (4), comprising:
  • a method for producing a compound of formula (6) as a step for producing the compound of formula (4), comprising:
  • a method for producing a compound of formula (6) as a step for producing the compound of the formula (4), comprising a step that the compound of the formula (1) is reacted with isobutylene under the existence of an acid catalyst.
  • said method further including a step that wherein compound of formula (6) is hydrolyzed under the existence of an acid and subjected to decarboxylation.
  • said method comprising:
  • R 1 representing C 1-4 alkyl group, arylmethyl group, or substituted arylmethyl group
  • R 2 representing C 1-4 alkyl group, arylmethyl group, or substituted arylmethyl group
  • the precursor compound on the process for synthesizing 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid which is a production intermediate of L-AMPB, which is useful as the herbicide, can be produced due to the producing method of the present invention.
  • the producing method of the present invention is superior to the conventional method in a low-cost and efficiency. Therefore, the present invention is extremely industrially useful, especially in the field of pharmaceuticals needed for herbicidal action.
  • C 1-4 alkyl groups shown as R 1 and R 2 mean straight chain or branched alkyl group having 1-4 carbons, in more detail, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, 2-butyl group, isobutyl group, t-butyl group and the like are listed.
  • the arylmethyl group represented by R 1 and R 2 means methyl group which is substituted by 1 to 3 aryl groups, in more detail, benzyl group, diphenylmethyl group, fluorenyl group, triphenylmethyl group and the like are listed.
  • the substituted arylmethyl group represented by R 1 and R 2 means that one or more hydrogen atom on benzene ring is substituted, preferably 1 to 3 hydrogen atoms are substituted; as a concrete substituted group(s), straight chain or branched C 1-4 alkyl group such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, 2-butyl group, isobutyl group, t-butyl group and the like; halogen atom such as fluorine atom, chromium atom, bromine atom and the like; and C 1-4 alkoxy group such as methoxy group and the like; are listed.
  • R 1 and R 2 are C 1-4 alkyl group, and more preferably methyl group and ethyl group.
  • the compound of formula (1) can be synthesized by the methods described in JP Kokai Publication 2004-345963A and JP Kokai Publication H05-247068A. (Disclosures of these documents are incorporated herein by references thereto.)
  • ethanol methanol, n-propanol, isopropyl alcohol, n-butanol, benzyl alcohol, and p-methylbenzyl alcohol are listed, and preferably, methanol.
  • methyl iodide ethyl iodide, n-propyl bromide, n-butyl bromide, benzyl bromide, benzyl chloride, and p-methylbenzyl bromide are listed, and more preferably, methyl iodide.
  • oxalic acid dimethylester oxalic acid diethylester, oxalic acid di n-propylester, oxalic acid n-butylester, oxalic acid dibenzylester or oxalic acid di p-methylbenzylester are listed, and oxalic acid dimethylester is preferable.
  • a compound shown below is preferable.
  • the compound of formula (6) has a relation of tautomer with a compound shown by the following formula (6′),
  • the compound of formula (6) and the compound of formula (6′) are existing in equilibrium in a solution. Thereby, in the case where the compound of formula (6) is indicated, it is considered that the compound of formula (6) also includes the structure of the tautomer of the compound of formula (6′).
  • halogenated hydrocarbon-based solvent such as methylene chloride and chloroform etc.
  • aromatic hydrocarbon-based solvents such as benzene and toluene etc.
  • alcohol solvent of formula (2) or mixed solvents including these two or more than two kinds of solvents described in the above are listed, and preferably, alcohol solvent of formula (2) and mixed solvent of formula (2) and benzene are listed.
  • the amount to be used of the acid is 0.01 to 0.3 equivalents based on the amount of the compound of formula (1).
  • the used amount of the compound shown by the formula (2) is 3 to 10 equivalents based on an amount of the compound of formula (1).
  • the reaction temperature is 0 to 130° C., and preferably, the reaction is performed within a range of 20 and 90° C.
  • the reaction time is generally 0.1-20 hours, and preferably, the reaction is performed within a range of 0.5 and 10 hours.
  • the generated water is separated by azeotropic distillation using Dean-Stark water separating apparatus, if necessary.
  • reaction solution After finish of the reaction, the reaction solution is concentrated or neutralized with alkali, then generated salt is removed. Thereafter, the compound of formula (4) can be isolated by concentrating the reaction solution. Usually, the reaction solution is used for the next step without the isolation.
  • the producing method of the compound of formula (4) from the compound of formula (1) and the compound of formula (2) under the existence of condensation agent and base is preferably applied to the case where the compound of formula (4) is manufactured from the compound of formula (2) in which R 1 is t-butyl group.
  • Halogenated hydrocarbon-based solvent such as methylene chloride, chloroform etc.; aromatic hydrocarbon-based solvents such as benzene, toluene etc.; ether based solvents such as tetrahydrofuran, dimethoxyethane, dioxane etc.; ester based solvent such as ethyl acetate etc.; aprotic polar organic solvents such as N,N-dimethyl formamide dimethyl sulfoxide etc.
  • the used amount of the compound shown by formula (2) is 1 to 2 equivalents based on the amount of the compound of formula (1).
  • the reaction temperature is 0 to 130° C., and preferably, the reaction is performed within a range of 10 and 30° C.
  • the reaction time is generally 1-20 hours, and preferably, the reaction is performed within a range of 3 and 12 hours.
  • the compound of formula (4) in which R 1 is t-butyl group when manufactured, it can be manufactured by reacting the compound of formula (1) and isobutylene under the existence of an acid catalyst.
  • Halogenated hydrocarbon-based solvents such as methylene chloride, chloroform etc.;, aromatic hydrocarbon-based solvents such as benzene, toluene, etc.; ether based solvents such as dimethoxyethane and dioxane are listed as solvents used in this reaction, and preferably, methylene chloride is listed.
  • the acid catalyst to be used concentrated sulfuric acid is listed. Isobutylene is used in an excess amount based on the amount of the compound of formula (1).
  • the used amount of the acid is 0.05 to 0.2 equivalents based on the amount of the compound of formula (1).
  • the reaction temperature is 0 to 50° C., and preferably, the reaction is performed within a range of 20 and 30° C.
  • the reaction time is usually within a range of 1-48 hours, and preferably, the reaction is performed within a range of 12 and 24 hours.
  • halogenated hydrocarbon-based solvent such as methylene chloride, chloroform etc.
  • aromatic hydrocarbon-based solvents such as benzene, toluene etc.
  • ether based solvents such as tetrahydrofuran, dimethoxyethane, dioxane etc.
  • ketone based solvents such as acetone etc.
  • aprotic polar organic solvents such as N,N-dimethyl formamide and dimethyl sulfoxide
  • alkanol solvents having 1-4 carbons such as methanol etc.
  • acetone, tetrahydrofuran, N,N-dimethyl formamide and dimethyl sulfoxide are listed, and preferably, acetone, tetrahydrofuran, N,N-dimethyl formamide and dimethyl sulfoxide are listed.
  • bases to be used sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, cesium carbonate, triethylamine and diisopropylethylamine etc. are listed, and preferably, sodium hydrocarbonate is listed.
  • the used amount of the base is 2 to 2.2 equivalents based on the amount of the compound of formula (1).
  • the used amount of the compound shown by the formula (3) is 1 to 1.2 equivalents based on the amount of the compound of formula (1).
  • the reaction temperature is 0 to 100° C., and preferably, the reaction is performed within a range of 0 and 30° C.
  • the reaction time is usually within a range of 0.5-24 hours, and preferably, the reaction is performed within a range of 1 and 10 hours.
  • halogenated hydrocarbon-based solvents such as methylene chloride, chloroform etc.
  • aromatic hydrocarbon-based solvents such as benzene, toluene etc., ether based solvents such as tetrahydrofuran, dimethoxyethane, dioxane etc.
  • aprotic polar organic solvents such as N,N-dimethyl formamide, dimethyl sulfoxide etc.
  • alkanol solvents having 1-4 carbons such as methanol etc.
  • sodium hydride, potassium hydride, sodium methoxide, sodium ethoxide, potassium t-butoxide etc. are listed, and preferably, sodium methoxide is listed.
  • the used amount of the base is 2 to 3 equivalents based on the amount of the compound of formula (4).
  • the amount of use of the compound shown by formula (5) is 1 to 1.6 equivalents based on the amount of the compound of formula (4).
  • the reaction temperature is 0 to 100° C., and preferably, the reaction is performed within a range of 40 and 60° C.
  • the reaction time is usually 0.5-12 hours, and preferably, the reaction is performed within a range of 1 and 7 hours.
  • reaction solution After finish of the reaction, the reaction solution is vacuum concentrated after neutralization of the base with diluted hydrochloric acid, and the compound of formula (6) can be isolated by purifying silica gel chromatography. After obtaining crude product by distilling away the reaction solvent; usually, the reaction solution is used for the next step without isolation.
  • hydrochloric acid and sulfuric acid are listed as acids used, and water is listed as a solvent.
  • concentration of acid is in a range of 6-12 N within the case where hydrochloric acid is used and in a range of 2-18 N in the case where sulfuric acid is used.
  • the reaction temperature is within a range of 20 to 150° C., and preferably, within a range of 50 to 120° C.
  • the reaction time is within a range of 2 to 12 hours, and preferably, in a range of 4 to 8 hours.
  • the compound (7) can be isolated and purified using an ion exchange resin (BIO-RAD (registered TRADEMARK) Ag 1 ⁇ 2, eluent: 1% trifluoro acetate aqueous solution), for example.
  • BIO-RAD registered TRADEMARK
  • Ag 1 ⁇ 2 eluent: 1% trifluoro acetate aqueous solution
  • 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid which is obtainable by the present invention can be converted to L-AMPB according to methods described in JP Kokai Publication H01-027485A, JP Kohyo Publication 2003-528572A, JP Kokai Publication S62-226993A and the like. (Disclosures of these documents are incorporated herein by reference thereto.)
  • a solution obtained by dissolving dimethyl oxalate (850 mg) in toluene (2 ml) was added to a mixed solution of 28% sodium methoxide (2.89 g) and toluene (3 ml) under ice-cold condition. After stirring for 10 minutes under ice-cold condition, a solution obtained by dissolving methyl 3-(hydroxy)(methyl)phosphinyl) propionate (996 mg) was dissolved in toluene (1 ml) was added. After stirring for 10 minutes under ice-cold condition, the resultant solution was heated to 50° C. and stirred for 5 hours.
  • APIMASS m/z 253 [M+H] +

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
US12/530,022 2007-03-23 2008-03-21 Method for producing phosphorus-containing α-keto acid Expired - Fee Related US8017797B2 (en)

Applications Claiming Priority (3)

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JP2007076541 2007-03-23
JP2007-076541 2007-03-23
PCT/JP2008/055206 WO2008117733A1 (ja) 2007-03-23 2008-03-21 リン含有α－ケト酸の製造法

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US8017797B2 true US8017797B2 (en) 2011-09-13

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US (1) US8017797B2 (de)
EP (1) EP2133356B1 (de)
JP (1) JP5368971B2 (de)
CN (2) CN101641363A (de)
ES (1) ES2525798T3 (de)
IL (1) IL200945A (de)
WO (1) WO2008117733A1 (de)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8481779B2 (en) 2010-06-15 2013-07-09 Meiji Seika Pharma Co., Ltd. Method for producing N-substituted-2-amino-4-(hydroxymethylphosphinyl)-2-butenoic acid
WO2019192505A1 (zh) 2018-04-03 2019-10-10 上海弈柯莱生物医药科技有限公司 一种l-谷氨酸脱氢酶突变体及其应用
WO2020233451A1 (zh) 2019-05-23 2020-11-26 弈柯莱生物科技(上海)股份有限公司 一种l-谷氨酸脱氢酶突变体及其应用

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CN103665032B (zh) * 2013-12-09 2016-02-17 江苏七洲绿色化工股份有限公司 一种草铵膦的制备方法
CN105175443B (zh) * 2015-08-17 2017-04-19 湖南海利化工股份有限公司 一种含磷α酮酸酯的制备方法
CN106279270A (zh) * 2016-08-08 2017-01-04 安徽国星生物化学有限公司 一锅法制备4‑(甲基羟基磷酰基)‑2‑羰基丁酸的方法
CN109369710B (zh) * 2018-10-26 2020-10-09 洪湖市一泰科技有限公司 一种4-(甲基羟基磷酰基)-2-羰基丁酸的高效纯化工艺
CN111690002A (zh) * 2020-04-29 2020-09-22 洪湖市一泰科技有限公司 锂盐化合物及其制备方法和包含其的锂离子电池电解液
CN117700451A (zh) * 2022-09-08 2024-03-15 浙江新安化工集团股份有限公司 一种4-(羟基甲基膦酰基)-2-羰基丁酸的制备方法
CN117700450A (zh) * 2022-09-08 2024-03-15 浙江新安化工集团股份有限公司 一种4-(羟基甲基膦酰基)-2-羰基丁酸的制备方法

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8481779B2 (en) 2010-06-15 2013-07-09 Meiji Seika Pharma Co., Ltd. Method for producing N-substituted-2-amino-4-(hydroxymethylphosphinyl)-2-butenoic acid
WO2019192505A1 (zh) 2018-04-03 2019-10-10 上海弈柯莱生物医药科技有限公司 一种l-谷氨酸脱氢酶突变体及其应用
WO2020233451A1 (zh) 2019-05-23 2020-11-26 弈柯莱生物科技(上海)股份有限公司 一种l-谷氨酸脱氢酶突变体及其应用

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IL200945A0 (en) 2010-05-17
JPWO2008117733A1 (ja) 2010-07-15
IL200945A (en) 2012-05-31
WO2008117733A1 (ja) 2008-10-02
EP2133356B1 (de) 2014-09-24
CN101641363A (zh) 2010-02-03
ES2525798T3 (es) 2014-12-30
CN104761583A (zh) 2015-07-08
JP5368971B2 (ja) 2013-12-18
EP2133356A4 (de) 2011-08-17
US20100063313A1 (en) 2010-03-11
EP2133356A1 (de) 2009-12-16

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